Temozolomide, Thalidomide, and Whole Brain Radiation Therapy for Patients With Brain Metastasis From Metastatic Melanoma A Phase II Cytokine Working Group Study
Temozolomide, Thalidomide, and Whole Brain Radiation Therapy for Patients With Brain Metastasis From Metastatic Melanoma A Phase II Cytokine Working Group Study
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DOI：
10.1002/cncr.23805
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发表时间：
2008-10-15
期刊：
影响因子：
6.2
通讯作者：
Margolin, Kim A.
中科院分区：
文献类型：
--
作者：
Atkins, Michael B.;Sosman, Jeffrey A.;Margolin, Kim A.
背景。据报道，替莫唑胺（TMZ）和沙利度胺联合使用在转移性黑色素瘤患者中产生了很高的反应率，包括脑转移灶的缩小。作者测试了包括TMZ、沙利度胺和全脑放射治疗（WBRT）在内的治疗方案对黑色素瘤脑（CNS）转移患者的疗效。有核磁共振记录的中枢神经系统转移的黑色素瘤患者，之前没有接受过全身化疗的患者接受WBRT， 30 Gray分10次，第1 - 5天和第8 - 12天；TMZ, 75 mg/m(2)/天，第1 ~ 6周；沙利度胺，100 mg/天，第1至4周，然后在第5、7和9周逐渐增加100 mg/天，直至耐受最大值为400 mg/天。在第10周评估中枢神经系统和全身肿瘤反应。没有中枢神经系统或临床显著的全身性疾病进展的患者每隔10周接受额外的TMZ治疗周期。39例患者接受治疗，3例出现中枢神经系统缓解（1例完全缓解，2例部分缓解）（缓解率7.6%，95%可信区间0.7%-16.1%），均未经重复影像学证实。7例患者在10周时中枢神经系统疾病稳定。没有患者表现出全身反应。只有4例患者接受了2个周期的治疗，只有1例接受了3个周期的治疗。中位进展时间为7周，中位总生存期为4个月。3-4级副作用包括深静脉血栓形成(3)、肺栓塞(1)和中枢神经系统事件（12）。18例（45%）患者因副作用（7例）和/或症状性疾病进展（11例）而入院。TMZ、沙利度胺和WBRT治疗中枢神经系统转移性黑色素瘤的疗效较低。对于这一患者群体，应考虑其他治疗方法。癌症2008;113:2139-45。(C) 2008年美国癌症协会。
BACKGROUND. The combination of temozolomide (TMZ) and thalidomide was reported to produce a high response rate, including shrinkage of brain metastases, in patients with metastatic melanoma. The authors tested the efficacy of a regimen including TMZ, thalidomide, and whole brain radiation therapy (WBRT) in patients with brain (CNS) metastases from melanoma.METHODS. Patients with melanoma, CNS metastases documented by magnetic resonance imaging, and no prior systemic chemotherapy received WBRT, 30 Gray in 10 fractions, Days 1 to 5 and 8 to 12; TMZ, 75 mg/m(2)/day, Weeks 1 to 6; and thalidomide, 100 mg/day, Weeks 1 to 4, then escalated by 100 mg/day at Weeks 5, 7, and 9 as tolerated to a maximum of 400 mg/day. CNS and systemic tumor response was assessed at Week 10. Patients without CNS or clinically significant systemic disease progression received additional cycles of TMZ at 10-week intervals.RESULTS. Thirty-nine patients received treatment, and 3 exhibited CNS response (1 complete response, 2 partial responses) (response rate, 7.6%; 95% confidence interval, 0.7%-16.1%), all unconfirmed by repeat imaging. Seven patients had stable CNS disease at 10 weeks. No patient exhibited a systemic response. Only 4 patients received 2 cycles of therapy, and just 1 received 3. Median time to progression was 7 weeks, and median overall survival was 4 months. Grade 3-4 side effects included deep venous thrombosis (3), pulmonary embolism (1), and CNS events (12). Eighteen (45%) patients required admission for side effects (7) and/or symptomatic disease progression (11).CONCLUSIONS. The efficacy of TMZ, thalidomide, and WBRT in the treatment of CNS metastatic melanoma is low. Other treatment approaches should be considered for this patient population. Cancer 2008;113:2139-45. (C) 2008 American Cancer Society.